§ To prevent patient pain, the clinician may chose from opioid and nonopioid analgesics. It is rational for the practitioner to combine drugs from these classes when managing moderate to severe pain.
The primary feature that distinguishes these 2 classes of analgesics is their mechanisms of action. Nonopioids include acetaminophen and the nonsteroidal anti-inflammatory drugs (NSAIDs), which interrupt prostaglandin synthesis and have a maximal dose or ceiling for their analgesic effect. Opioids, as represented by morphine, act as agonists at 3 specific receptors designated mu, kappa, and delta. The fact that opioids have no dose limit or ceiling permits their dose to be increased until relief is obtained, or limiting side effects occur. It is rational for the practitioner to combine drugs from these classes when managing moderate to severe pain. To select combination regimens wisely, it is necessary to understand the significant pharmacological features of each category alone. § Pain controlling effect – Nonopioid analgesics, antipyretics, and NSAIDs are a broad group of pain medication. They also produce fever control and anti-inflammatory effects. They can be used alone or as adjuvant medications. These drugs have a ceiling effect, and no physical dependence is associated with them. § Drug classes: salicylates, acetaminophen, NSAIDs.
§ Salicylates- are the most commonly used pain medications. Used to control pain, reduce fever, and inflammation. · Mechanism of action- They relieve pain primarily by inhibiting the synthesis of prostaglandin. (recall that prostaglandins are a chemical mediator that sensitizes nerve cells to pain) In addition they may reduce inflammation by inhibiting prostaglandin synthesis and release that occurs during inflammation. Salicylates reduce fever by stimulating the hypothalamus and producing peripheral blood vessel dilation and increased sweating. These promote heat loss through the skin and cooling by evaporation. Also, because prostaglandin E increases body temperature, inhibiting its production lowers fever. One salicylate (aspirin) inhibits platelet aggregation (the clumping of platelets to form a clot) by interfering with the production of thromboxane A2, a substance necessary for platelet aggregation. Unlike aspirins, NSAIDs effects on platelet aggregation are temporary. As a result, aspirin can be used to enhance blood flow during myocardial infarction and to prevent an event such as recurrent MI. · Pharacokinetics- Taken orally, salicylates are partially absorbed in the stomach but are primarily absorbed in the upper part of the small intestine. The pure and buffered forms of aspirin reabsorb readily, but sustained released and coated salicylate preparations or food or anti-acids in the stomach delay absorption. Coated products are slowly absorbed and not suitable for acute effects, but they cause less GI bleeding and are better for long term therapy. · Pharmacologic effects- Salicylates are primarily used to relieve pain and reduce fever. However, they don’t effectively relieve visceral pain (pain from the organs and smooth muscle) or severe pain from trauma. They can also be used to reduce elevated body temperature in conjunction with relieving headache and muscle ache. When used to reduce inflammation in rheumatic fever, rheumatoid arthritis, and osteoarthritis, salicylates can provide considerable relief within 24 hours. Use lowest dose that provides relief. · Toxicity- Because salicylates are highly protein bound, they can interact with many other protein-bound drugs by displacing those drugs from sites to which they normally bind. This increases the serum concentration of the unbound active drug, causing increased pharmacologic effects. · Drug interactions- Oral anticoagulants, heparin, methotrexate, oral antidiabetic agents, and insulin are among the drugs that have increased effects or risk of toxicity. · Uses- Pain relief, anti-inflammatory, fever reducer, prevention of MI, management of postoperative pain, gout , arthritis · Dosage- for an adult 325-650mg every 4/6 hours · Preparations- pure, buffered, sustained release, and enteric-coated § Example of a Salicylates and its uses: § Aspirin Aspirin - Acetic Acid + Salicylic Acid
It inhibits prostaglandins involved in the production of inflammation and pain.
Has antpyretic action.
Inhibits platelet aggregation.
Dilates blood vessels.
Relieves pain that is caused by arthritis and rheumatoid arthritis.
Given to patients as a preventive for MI and CVA.
Most effective and rapid onset if administered on an empty stomach.
Contraindicated with patients that have bleeding disorders like anemia and hemophilia.
Contraindicated in children 12 years old and younger due to risk of Reye's syndrome.
Contraindicated with pregnant women.
Contraindicated with patients that have peptic ulcers, renal or hepatic diseases.
Increased bleeding with consumptions of anticoagulants and alcohol.
§ Acetaminophen: OTC drug that produces analgesic (pain) and antipyretic (fever) effects. It is found in many products designed to relieve pain and symptoms associated with colds and influenza (flu) · Pharmacokinetics- Acetaminophen is absorbed rapidly and completely from the GI tract. It’s also absorbed well from the mucous membranes of the rectum. It is widely distributed in the body fluids and readily crosses the placenta. After the liver metabolizes acetaminophen, it’s excreted by the kidneys and in small amounts in breast milk. · Pharmacologic effects- Acetaminophen reduces pain and fever but unlike salicylates it doesn’t affect inflammation or platelet function. The pain control effects of acetaminophen work in the CNS by inhibiting prostaglandin synthesis. It reduces fever by acting directly on the heat regulating center in the hypothalamus. · Adverse effects- Most patients tolerate acetaminophen well. Unlike the salicylates, acetaminophen rarely causes gastric irritation or bleeding tendencies. However it may cause liver toxicity and the total daily dose should be monitored. Other reactions are: skin rash, hypoglycemia (low sugar), and neutropenia (Decrease in WBC) · Drug interactions- It may slightly increase the effects of oral anticoagulants such as warfarin. The risk of liver toxicity is increased when barbiturates are combined and also with chronic alcohol use. · Uses- to reduce fever and relieve headache, muscle ache, and general pain. § Example of a acetaminophen and its uses § Tylenol Antipyretic action
Used to reduce pain or fever if patient has an allergic reaction to aspirin or NSAIDs.
Taken with alcohol can increase risk of liver damage.
Should not be taken at the same time as aspirin.
§ Nonsteroidal anti-inflammatory agents or drugs (NSAIDS): · Chemical classification: Mechanism of action: Results in their ability to inhibit COX activity, thereby preventing the synthesis and release of COX products, most prominently the prostaglandins. These drugs are potent or at least equipotent inhibitors of COX-1, which accounts for some of the more important adverse reaction for these drugs. Other mechanism contributing to anti-inflammatory effects may include reduced capillary permeability, reduced antibody production, and alteration in connective tissue synthesis. · Pharmacokinetics: All NSAIDS are absorbed in the GI tract. They’re mostly metabolized in the liver and excreted primary in the kidneys. · Pharmacologic effects Adverse reactions: Adverse reaction can include abdominal pain and bleeding, anorexia, diarrhea, nausea, ulcers, liver toxicity, drowsiness, headache, hypertension confusion, and blood in urine. Can also effect anti-platelet effects causing prolong bleeding. · Contraindication: Serious internal bleeding can result from the ingestion of aspirin by a patient with an ulcer, compromised liver function. · Cautions: Not absolutely contraindicated in pregnancy but should be used with caution. · Uses: Primarily used to decrease inflammation. They are also used to relieve pain but are seldom prescribed to reduce fever. Moderate to severe rheumatiod arthritis, migraines, mild to moderate pain. § Example of an NSAID and its uses: Ibuprofen
Drug interactions with NSAIDS:
ACE inhibitors- Captopril
Potential outcomes include: decrease in antihypertensive effects
Beta-Blockers-
Potential outcomes include: decrease in antihypertensive effects
Diuretics
Thiazide, furosemide, triamterene- Potential outcomes include: decrease in antihypertensive and diuretic effects
Warfarin- increase risk of bleeding
Lithium- increase risk of lithium toxicity
Digoxin- increase risk of digoxin toxicity
Phenytoin- increase risk of phenytoin toxicity
Sympathomimetics- increase risk of antihypertensive effects
Cyclosporin- nephrotoxicity
Methotrexate- increase methotrexate toxicity, less problem with rheumatoid arthritis doses
Probenecid- increase NSAIDS level, okay with caution
Salicylates- decrease NSAIDS blood level, ok to continue 1/day for anticlotting effect
Corticosteroids- decrease ulcerogenic risk
Antidiabetics- increase risk of hypogycemia
See full size image
Decrease prostaglandins
Anti-inflammatory drug.
Fever reducer.
Treat mild pain due to arthritis.
Treat mild pain also associated with rheumatoid arthritis.
Can be taken for gout.
Can be use as an anticoagulant.
Must be taken with water, milk or food to decrease gastric irritation.
Contraindicated with patients that have asthma.
Drugs that affect serotonin, which leads to pain relief Triptans, such as sumatriptan, are 5-HT1b and 5HT1d receptor agonists and these receptors are located in the blood vessels of the cranium. Triptans causes these blood vessels to constrict and prevents an inflammatory response and thus alleviate severe migraines.
TCAs, such as amitriptyline, are antidepressants that have been shown to relieve pain. TCAs may inhibit pain due to its 5-HT receptor activity for the pre- and post-synaptic neurons. TCAs may downregulate 5-HT2 receptors which have been link to promoting inflammation.
Anitgout medication
What is gout? A painful inflammation of the big toe and foot caused by defects in the uric acid metabolism resulting in deposits of the acid and its salts in the blood and joints.
Medication for gout include:
non-steroidal anti-inflammatory drugs (NSAIDS)- specifically indomethacin, are commonly the first medication prescribed to treat acute gout. Other NSAIDS may be equally effective. NSAIDS are initially prescribed at maximum dosage and reduced as symptoms subside. The medication should be continued until pain and inflammation are non-existent for at least 48 hours. NSAIDS which are Cox2 inhibitors may be useful for patients with gastrointestinal concerns but their use for acute gout has not been specifically reported yet.
colchicine
corticosteroids
adrenocorticotropic hormone (ACTH)
allopurinol
probenecid
sulfinpyrazone
Gout is often related to an inherited abnormality in the body to process uric acid. Uric acid levels can become elevated by eating a lot of purine-rich foods such as meats, by the overproduction of uric acid by the body, or if the kidneys do not eliminate excess uric acid.
Treatment goals include terminating acute gout attacks, rapid and safe relief of pain and inflammation, preventing future attacks, and avoiding complications (formation of tophi, kidney stones, and joint destruction).
Nonopioid analgesics
§ To prevent patient pain, the clinician may chose from opioid and nonopioid analgesics. It is rational for the practitioner to combine drugs from these classes when managing moderate to severe pain.
The primary feature that distinguishes these 2 classes of analgesics is their mechanisms of action. Nonopioids include acetaminophen and the nonsteroidal anti-inflammatory drugs (NSAIDs), which interrupt prostaglandin synthesis and have a maximal dose or ceiling for their analgesic effect. Opioids, as represented by morphine, act as agonists at 3 specific receptors designated mu, kappa, and delta. The fact that opioids have no dose limit or ceiling permits their dose to be increased until relief is obtained, or limiting side effects occur. It is rational for the practitioner to combine drugs from these classes when managing moderate to severe pain. To select combination regimens wisely, it is necessary to understand the significant pharmacological features of each category alone.
§ Pain controlling effect – Nonopioid analgesics, antipyretics, and NSAIDs are a broad group of pain medication. They also produce fever control and anti-inflammatory effects. They can be used alone or as adjuvant medications. These drugs have a ceiling effect, and no physical dependence is associated with them.
§ Drug classes: salicylates, acetaminophen, NSAIDs.
§ Salicylates- are the most commonly used pain medications. Used to control pain, reduce fever, and inflammation.
· Mechanism of action- They relieve pain primarily by inhibiting the synthesis of prostaglandin. (recall that prostaglandins are a chemical mediator that sensitizes nerve cells to pain) In addition they may reduce inflammation by inhibiting prostaglandin synthesis and release that occurs during inflammation. Salicylates reduce fever by stimulating the hypothalamus and producing peripheral blood vessel dilation and increased sweating. These promote heat loss through the skin and cooling by evaporation. Also, because prostaglandin E increases body temperature, inhibiting its production lowers fever. One salicylate (aspirin) inhibits platelet aggregation (the clumping of platelets to form a clot) by interfering with the production of thromboxane A2, a substance necessary for platelet aggregation. Unlike aspirins, NSAIDs effects on platelet aggregation are temporary. As a result, aspirin can be used to enhance blood flow during myocardial infarction and to prevent an event such as recurrent MI.
· Pharacokinetics- Taken orally, salicylates are partially absorbed in the stomach but are primarily absorbed in the upper part of the small intestine. The pure and buffered forms of aspirin reabsorb readily, but sustained released and coated salicylate preparations or food or anti-acids in the stomach delay absorption. Coated products are slowly absorbed and not suitable for acute effects, but they cause less GI bleeding and are better for long term therapy.
· Pharmacologic effects- Salicylates are primarily used to relieve pain and reduce fever. However, they don’t effectively relieve visceral pain (pain from the organs and smooth muscle) or severe pain from trauma. They can also be used to reduce elevated body temperature in conjunction with relieving headache and muscle ache. When used to reduce inflammation in rheumatic fever, rheumatoid arthritis, and osteoarthritis, salicylates can provide considerable relief within 24 hours. Use lowest dose that provides relief.
· Toxicity- Because salicylates are highly protein bound, they can interact with many other protein-bound drugs by displacing those drugs from sites to which they normally bind. This increases the serum concentration of the unbound active drug, causing increased pharmacologic effects.
· Drug interactions- Oral anticoagulants, heparin, methotrexate, oral antidiabetic agents, and insulin are among the drugs that have increased effects or risk of toxicity.
· Uses- Pain relief, anti-inflammatory, fever reducer, prevention of MI, management of postoperative pain, gout , arthritis
· Dosage- for an adult 325-650mg every 4/6 hours
· Preparations- pure, buffered, sustained release, and enteric-coated
§ Example of a Salicylates and its uses:
§ Aspirin
Aspirin - Acetic Acid + Salicylic Acid
It inhibits prostaglandins involved in the production of inflammation and pain.
Has antpyretic action.
Inhibits platelet aggregation.
Dilates blood vessels.
Relieves pain that is caused by arthritis and rheumatoid arthritis.
Given to patients as a preventive for MI and CVA.
Most effective and rapid onset if administered on an empty stomach.
Contraindicated with patients that have bleeding disorders like anemia and hemophilia.
Contraindicated in children 12 years old and younger due to risk of Reye's syndrome.
Contraindicated with pregnant women.
Contraindicated with patients that have peptic ulcers, renal or hepatic diseases.
Increased bleeding with consumptions of anticoagulants and alcohol.
§ Acetaminophen: OTC drug that produces analgesic (pain) and antipyretic (fever) effects. It is found in many products designed to relieve pain and symptoms associated with colds and influenza (flu) · Pharmacokinetics- Acetaminophen is absorbed rapidly and completely from the GI tract. It’s also absorbed well from the mucous membranes of the rectum. It is widely distributed in the body fluids and readily crosses the placenta. After the liver metabolizes acetaminophen, it’s excreted by the kidneys and in small amounts in breast milk.
· Pharmacologic effects- Acetaminophen reduces pain and fever but unlike salicylates it doesn’t affect inflammation or platelet function. The pain control effects of acetaminophen work in the CNS by inhibiting prostaglandin synthesis. It reduces fever by acting directly on the heat regulating center in the hypothalamus.
· Adverse effects- Most patients tolerate acetaminophen well. Unlike the salicylates, acetaminophen rarely causes gastric irritation or bleeding tendencies. However it may cause liver toxicity and the total daily dose should be monitored. Other reactions are: skin rash, hypoglycemia (low sugar), and neutropenia (Decrease in WBC)
· Drug interactions- It may slightly increase the effects of oral anticoagulants such as warfarin. The risk of liver toxicity is increased when barbiturates are combined and also with chronic alcohol use.
· Uses- to reduce fever and relieve headache, muscle ache, and general pain.
§ Example of a acetaminophen and its uses
§ Tylenol
Antipyretic action
Used to reduce pain or fever if patient has an allergic reaction to aspirin or NSAIDs.
Taken with alcohol can increase risk of liver damage.
Should not be taken at the same time as aspirin.
§ Nonsteroidal anti-inflammatory agents or drugs (NSAIDS):
· Chemical classification: Mechanism of action: Results in their ability to inhibit COX activity, thereby preventing the synthesis and release of COX products, most prominently the prostaglandins. These drugs are potent or at least equipotent inhibitors of COX-1, which accounts for some of the more important adverse reaction for these drugs. Other mechanism contributing to anti-inflammatory effects may include reduced capillary permeability, reduced antibody production, and alteration in connective tissue synthesis.
· Pharmacokinetics: All NSAIDS are absorbed in the GI tract. They’re mostly metabolized in the liver and excreted primary in the kidneys.
· Pharmacologic effects Adverse reactions: Adverse reaction can include abdominal pain and bleeding, anorexia, diarrhea, nausea, ulcers, liver toxicity, drowsiness, headache, hypertension confusion, and blood in urine. Can also effect anti-platelet effects causing prolong bleeding.
· Contraindication: Serious internal bleeding can result from the ingestion of aspirin by a patient with an ulcer, compromised liver function.
· Cautions: Not absolutely contraindicated in pregnancy but should be used with caution.
· Uses: Primarily used to decrease inflammation. They are also used to relieve pain but are seldom prescribed to reduce fever. Moderate to severe rheumatiod arthritis, migraines, mild to moderate pain.
§ Example of an NSAID and its uses:
Ibuprofen
Drug interactions with NSAIDS:
Decrease prostaglandins
Anti-inflammatory drug.
Fever reducer.
Treat mild pain due to arthritis.
Treat mild pain also associated with rheumatoid arthritis.
Can be taken for gout.
Can be use as an anticoagulant.
Must be taken with water, milk or food to decrease gastric irritation.
Contraindicated with patients that have asthma.
Drugs that affect serotonin, which leads to pain relief
Triptans, such as sumatriptan, are 5-HT1b and 5HT1d receptor agonists and these receptors are located in the blood vessels of the cranium. Triptans causes these blood vessels to constrict and prevents an inflammatory response and thus alleviate severe migraines.
TCAs, such as amitriptyline, are antidepressants that have been shown to relieve pain. TCAs may inhibit pain due to its 5-HT receptor activity for the pre- and post-synaptic neurons. TCAs may downregulate 5-HT2 receptors which have been link to promoting inflammation.
Anitgout medication
What is gout? A painful inflammation of the big toe and foot caused by defects in the uric acid metabolism resulting in deposits of the acid and its salts in the blood and joints.
Medication for gout include:
Gout is often related to an inherited abnormality in the body to process uric acid. Uric acid levels can become elevated by eating a lot of purine-rich foods such as meats, by the overproduction of uric acid by the body, or if the kidneys do not eliminate excess uric acid.
Treatment goals include terminating acute gout attacks, rapid and safe relief of pain and inflammation, preventing future attacks, and avoiding complications (formation of tophi, kidney stones, and joint destruction).